Spatiotemporally controlled AuNPs@ZIF-8 based nanocarriers for synergistic photothermal/chemodynamic therapy.

High efficiency and spatio-temporal control remains a challenge for multi-modal synergistic cancer therapy. Herein, based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), a spatio-temporal controllable photothermal/ chemical dynamic/ chemotherapy three modal synergistic anti-tumor nano-carrier (HAZD) was developed. HAZD has a size of 128.75 ± 11.86 nm, a drug loading ratio of 21.5 ± 2.2 % and an encapsulation efficiency of 71.8 ± 1.7 %. Stability, acid responsive release character, outstanding catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 % and spatio-temporal controllable abilities are also found within this nano-carrier. Furthermore, HAZD performed good antitumor ability in vivo with the comprehensive effects of photothermal/ chemical dynamic/ chemotherapy. The tumor growth inhibition value is 97.1 % within 12 days, indicating its great potential in multi-modal synergistic cancer therapy. STATEMENT OF SIGNIFICANCE: Cancer remains one of the major culprits that seriously harm human health currently. With the development of materials and nanotechnology, great improvements have been made in multimodal anti-tumor strategies. However, temporal- and spatial-controllable multi-modal synergistic nanocarriers are urgently awaited for efficient and low-toxicity tumor therapy. This article proposes a spatio-temporally controllable three-modal anti-tumor strategy and designs an anti-tumor drug delivery system based on gold nanoparticles (AuNPs) and zeolite-like imidazole skeleton material (ZIF-8), which shows acid-responsive release characteristics, catalytic ability to generate ROS, relatively high thermal conversion efficiency up to 62.38 %, as well as spatio-temporal controllable abilities. Moreover, it demonstrates outstanding anti-tumor ability, with a tumor growth inhibition value of 97.1 % within 12 days, revealing its significant potential for future personalized and precise anti-tumor treatments.

Enhanced delivery of theranostic liposomes through NO-mediated tumor microenvironment remodeling.

Highly efficient delivery of nanoagents to the tumor region remains the primary challenge for cancer nanomedicine. Herein, we propose a NO-mediated tumor microenvironment (TME) remodeling strategy for the high-efficient delivery of nanoagents into tumor. Quantum dots (QDs) with bright fluorescence in the near-infrared IIb (NIR-IIb, 1500-1700 nm) window and high photothermal conversion efficiency were encapsulated into liposomes for the imaging-guided photothermal therapy (PTT) of tumor. The fabrication of PEG and arginine-glycine-aspartate (RGD) peptide on liposomes ensured the prolonged circulation in vivo and active targeting to tumor. Moreover, the loading of a natural NO generator L-arginine in liposomes realized the continuous generation of NO in the acidic TME. By co-localization fluorescence imaging and western blot of tumor tissue, we confirmed that the release of NO activated the expression of metalloproteinases in TME and further degraded Collagen I in the peripheral region of the tumor, thus removing the barrier for the permeation of liposomes. Attributed to the enhanced accumulation of liposomes inside the tumor, NIR IIb imaging-guided PTT was achieved with remarkable therapeutic efficacy.

Chemical compositions and pharmacological activities of natural musk (Moschus) and artificial musk: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Natural musk (Moschus), derived naturally from male musk deer (Moschus berezovskii Flerov, Moschus sifanicus Przewalski, or Moschus moschiferus Linnaeus), has long been an important component of traditional Chinese medicine (TCM), and was used as resuscitation, blood circulation, and collateral drainage. detumescence and pain relief. Artificial musk was researched and applied into TCM as natural musk being as unsustainable resources. AIM OF THE STUDY: We mainly summarized chemical compositions, pharmacological activities and mechanism of action of natural and artificial musk, and designed to serve as a foundation for further research into musk chemical compositions and pharmacological effect. MATERIALS AND METHODS: Those mainstream scientific databases including Google Scholar, ScienceDirect, SpringerLink, CNKI, Wiley Online Library, web of science, were used for searching with below "Keywords", as well as literature-tracking. Literatures spanned 1962 to 2021, and involved into Chinese, English, Janpanese, Korean. RESULTS: Natural musk contains some very desirable but scarce compounds, as well as their biological features, which led to the development of artificial musk. The chemical ingredients, pharmacological activities, and mechanisms of action of natural and artificial musk are summarized and compared in this paper. Polypeptide and protein, muscone, musclide, steroids, muscopyridine, and other chemical constituents of musk demonstrated important therapeutic properties against inflammation, immune system disorders, neurological disorders, cardiovascular system disorders, and so on. The mechanism of action contributed to effect on mediators, acceptors and relative signal pathways. CONCLUSIONS: Natural and artificial musk were revealed having some activated compounds, and showed excellent pharmacological effect. Meantime, above two sides of natural and artificial musk ought to get further research.

Cichoric acid from witloof inhibit misfolding aggregation and fibrillation of hIAPP.

The misfolding, aggregation and fibrillation of human islet amyloid polypeptide (hIAPP) has been acknowledged as a hallmark event in type-II diabetes. Hence, inhibiting the misfolding, aggregation and fibrillation of hIAPP have been accepted as a vital factor to treat the disease. Here cichoric acid was extracted from witloof to explore its inhibition effects on misfolding, aggregation and fibrillation of hIAPP. Thioflavin-T (ThT) fluorescence assay, dynamic light scattering (DLS) and atomic force microscopy (AFM) images showed that cichoric acid inhibited the aggregation and fibrillation of hIAPP in a dosage-dependent manner. Circular dichroism (CD) spectra showed that cichoric acid inhibited the misfolding of hIAPP from unfolded to ß-sheet. Molecular docking and further experiments revealed interactions between hIAPP and cichoric acid. Cichoric acid could bind to K1 and R11 of hIAPP via electrostatic interaction. In addition, cichoric acid could form π-π stacking with hIAPP residues F15 and F23. These interactions inhibited the misfolding, aggregation and fibrillation of hIAPP. These results, together with cichoric acid's good cytocompatibility and significant protective effects in hIAPP lesioned cell models, not only showed that cichoric acid could be used to fight against amyloidosis, but also brought a new perspective for Chinese herbal medicine as natural compound's medical potential.

Olanzapine-induced endoplasmic reticulum stress and inflammation in the hypothalamus were inhibited by an ER stress inhibitor 4-phenylbutyrate.

Antipsychotics are the most important treatment for schizophrenia. However, antipsychotics, particularly olanzapine and clozapine, are associated with severe weight gain/obesity side-effects. Although numerous studies have been carried out to identify the exact mechanisms of antipsychotic-induced weight gain, it is still important to consider other pathways. Endoplasmic reticulum (ER) stress signaling and its associated inflammation pathway is one of the most important pathways involved in regulation of energy balance. In the present study, we examined the role of hypothalamic protein kinase R like endoplasmic reticulum kinase- eukaryotic initiation factor 2α (PERK-eIF2α) signaling and the inflammatory IkappaB kinase ß- nuclear factor kappa B (IKKß-NFκB) signaling pathway in olanzapine-induced weight gain in female rats. In this study, we found that olanzapine significantly activated PERK-eIF2α and IKKß-NFκB signaling in SH-SY5Y cells in a dose-dependent manner. Olanzapine treatment for 8 days in rats was associated with activated PERK-eIF2α signaling and IKKß-NFκB signaling in the hypothalamus, accompanied by increased food intake and weight gain. Co-treatment with an ER stress inhibitor, 4-phenylbutyrate (4-PBA), decreased olanzapine-induced food intake and weight gain in a dose- and time-dependent manner. Moreover, 4-PBA dose-dependently inhibited olanzapine-induced activated PERK-eIF2α and IKKß-NFκB signaling in the hypothalamus. These results suggested that hypothalamic ER stress may play an important role in antipsychotic-induced weight gain.

Chiral ß-HgS quantum dots: Aqueous synthesis, optical properties and cytocompatibility.

ß-HgS quantum dots (QDs) have drawn enormous attention due to the size-tunable bandgap and the lowest quantum state in conduction band which have been applied to semiconductor transistor and photodetector. Though ß-HgS is the essential component of Tibetan medicine, the potential toxicity of ß-HgS limits its applications, especially in bio-application. Herein, chiral biomolecule enantiomers N-isobutyryl-L(D)-cysteine (L(D)-NIBC) and L(D)-cysteine (L(D)-Cys) were introduced into HgCl2 and Na2S aqueous solution to synthesize chiral ß-HgS QDs in one-pot, which significantly improved their water-solubility and cytocompatibility. Notably, all chiral ß-HgS QDs showed none cytotoxicity even at high concentration (20 mg·L-1), and the cytocompatibility of D-ß-HgS QDs was better than corresponding L-ß-HgS QDs at the concentration of 20 mg·L-1. This cytotoxicity discrimination was associated with the chirality inversion of chiral ß-HgS QDs compared with the corresponding chiral ligands. In-situ real-time circular dichroism (CD) monitoring indicated that the chirality of ß-HgS QDs originated from the asymmetrical arrangement of chiral ligands on the achiral core surface. Their chiroptical activity, near-infrared optical absorption (800 nm), fluorescence emission (900-1000 nm), high-performance photothermal conversion and good cytocompatibility, implied chiral ß-HgS QDs could be used as a candidate material for photothermal therapy or a near-infrared fluorescent probe in organism, which brings a novel insight for bio-application of ß-HgS QDs.

Wettability switching between high hydrophilicity at low pH and high hydrophobicity at high pH on surface based on pH-responsive polymer.

Surfaces obtained by modifying poly(N,N'-dimethylaminoethyl methacrylate) (PDMAEMA) on rough silicon substrates are highly hydrophilic at low pH and highly hydrophobic at high pH; such surfaces effectively supplement the research on the wettability of solid surfaces based on the pH-responsive polymers.